Novel NEXMIF gene pathogenic variant in a female patient with refractory epilepsy and intellectual disability

We identified a novel nonsense de novo pathogenic variant of the NEXMIF gene in a 29 year-old female patient with refractory epilepsy and mild intellectual disability. The patient presented with episodic atypical absence status (AS), the longest duration of her seizures was approximately 36 hr. She also had occasional eyelid myoclonia during absence seizure. EEG highlighted a photosensitivity phenomenon and generalized epileptiform discharges that were induced by eye closure. Whole exome sequencing revealed a novel nonsense pathogenic variant c.1063delC (p.L355*) in exon 3 of the NEXMIF gene. The mRNA expression of NEXMIF in this female patient was below -2 SD from the mean of control group. In addition to adding a novel pathogenic variant type to the NEXMIF variant database and conducting mRNA studies, this report also describes a unique phenotype in a patient with atypical AS associated with a NEXMIF variant. We discuss implications for medication management in similar patients.